Cue-elicited prefrontal gamma-aminobutyric acid (GABA) dynamics in cannabis use disorder.

Gaillard A.; Fehring D.; Sumner P.; Randhawa A.; Rossell S. · Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026

**Background & Methods** This study used magnetic resonance spectroscopy (HERMES) to measure neurometabolites in the dorsolateral prefrontal cortex (dlPFC) during a cue reactivity paradigm in 22 individuals with cannabis use disorder (11 females) and 19 matched non-cannabis using controls (9 females). Participants were exposed to both cannabis-related and neutral cues while GABA+ and Glx levels were measured and analyzed using GANNET software. **Key Findings** - Individuals with cannabis use disorder and controls showed similar baseline GABA+ levels at rest, but demonstrated differential responses to cue reactivity - Cannabis users exhibited significant increases in GABA+ during cannabis cue exposure compared to neutral cue exposure (F1,16 = 7.31, p = 0.016, n2p = .31), independent of cue presentation order - Cue-elicited GABA dynamics were identified as a clinically relevant neurometabolic biomarker that may be amenable to therapeutic intervention and is not detectable under resting conditions **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This is a review article examining neurobiological mechanisms in cannabis use disorder rather than a clinical trial, limiting direct therapeutic conclusions. The relatively small sample size (n = 41 total) restricts generalizability. The cross-sectional design prevents determination of causality or temporal relationships between GABA dynamics and symptom severity. The study's primary strength is its novel application of cue-reactivity paradigms combined with magnetic resonance spectroscopy to detect dynamic neurometabolic changes invisible at baseline. This represents moderate evidence quality for identifying potential biomarkers but requires replication in larger, longitudinal cohorts. Future research should investigate whether cue-elicited GABA alterations predict treatment response or relapse risk, and whether interventions targeting GABAergic function can normalize these dynamics and reduce craving in cannabis use disorder.

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